In ten NIH-supported core projects conducted by the seven co- investigators of this proposal, Circular Dichroism (CD) spectropolarimetry provides a unique window into dynamic aspects of protein conformation, conformational transitions accompanying peptide- membrane interaction and insertion, nucleic acid-protein interaction, and investigations of the active conformation of drug molecules bound to their protein or nucleic acid targets. We seek to acquire a state-of- the-art CD spectropolarimeter to support and enhance these research programs. This instrument would replace an obsolete reconditioned instrument having only analog (chart paper) output and no programming or analysis capabilities, and which represents the sole CD resource for NIH-supported investigators in 7 departments and 4 divisions of this University who have extensive, demonstrable need, as well as experience with CD. The transition to modern instrumentation, which would provide digital data acquisition and computer-controlled experiment management, will not only enhance productivity by reducing the need for constant operator intervention, but also will make possible experimental approaches that are not feasible with the existing instrument. Repetitive scanning and digital averaging of spectra, accurate and programmable temperature control, stopped flow for kinetic studies, and an automated titrator for denaturation/refolding studies represent capabilities that will enhance greatly the existing NIH-supported projects.